Evaluating the impact of bone-targeted agents in the era of novel androgen targeted therapy for metastatic castration-resistant prostate cancer.

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e16500 Background: Patients with metastatic castrate resistant prostate cancer (mCRPC) often develop bone metastases, resulting in a risk of symptomatic skeletal events (SSE). Bone-targeted agent (BTA) has been integrated into the overall treatment strategy, but its role in the era of novel androgen-targeted therapy (ATT) is still unclear. Methods: A retrospective analysis of real-world practice from 2010 to 2015 was conducted. Patients diagnosed with mCRPC and bone metastases who received systemic therapy (docetaxel/abiraterone/enzalutamide) with or without BTA (zoledronic acid/denosumab/alendronate) were included. Results: We obtained data from 299 patients with a median follow-up of 75.5 months. Compared with no BTA, concomitant BTA was associated with decreased incident of SSE (3.8% vs. 19.2%, p< 0.001), especially in the need for bone radiation (1.9% vs. 15.8%, p< 0.001). Compared to patients without SSE, patients with SSE were more likely to have previous fracture history (10.8% vs. 9.7%, p= 0.047), steroid use history (2.4% vs. 1.4%, p= 0.019), smoking history (53.0% vs. 38.9%, p= 0.009), diabetes (19.3% vs. 8.8%, p= 0.012) and reduced baseline mobility (9.6% vs. 4.2%, p= 0.002). Among those who received first-line novel ATT (n = 152), concurrent ATT+BTA significantly decreased the incident of SSE (2.8% vs. 27.3%, p= 0.004) and prolonged the time to SSE (24.3 vs. 3.2 mo, p< 0.001), when compared to ATT alone. But there was no difference in overall survival between two groups (134.2 vs. 138.9 mo, p= 0.99). In patients who responded to systemic treatment with PSA declining, the SSE rate (2.4% vs. 14.3%, p= 0.037) was lower and the time to SSE was longer (49.6 vs. 32.3 mo, p= 0.026) than those who did not respond. Smoking history (adjusted HR = 1.46, p= 0.013) and PSA response (adjusted HR = 0.19, p< 0.001) are independent risk factors for SSE. Conclusions: This real-world database suggests that concomitant BTA with novel ATT was associated with reducing SSEs. PSA decrease might be used as a predictive factor for those under BTA treatment. Further studies are warranted to validate the role of PSA response.